Nephron Pharmaceuticals Corporation dba Nephron Sterile Compounding Center, LLC — FDA Warning Letter Findings

Your firm failed to conduct, for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(b)).

Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21CFR113(b)).

A USP <71> sterility test validation timeline for each product; 2. A (b)(4) discontinuation date; 3. An investigation into all the products that were associated with excess events; and 4. A determination of the impact on the sterility assurance of each of the effected products involved in the excess event excursions. Some of your corrective actions appear deficient: In response to observation 2 of the Form FDA 483, you stated that you have modified your environmental…

Laboratory records are deficient in that they do not include the initials and signature of the second person reviewing the record for accuracy (21 CFR 211.194 (a)(8)). Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing…

Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Your media fills were not performed under the most challenging or stressful conditions such as failing to simulate the largest batch size produced at your firm. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility. FDA investigators also noted CGMP violations at your facility, that caused your drug product(s) to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example…

You did not take appropriate corrective actions, nor did you perform adequate product evaluation after approximately 1686 excursions of microbial contamination were recovered within the ISO 5 aseptic processing area.

Your firm failed to maintain written production, control, or distribution records specifically associated with a batch of a drug product for at least one year after the expiration date of the batch (CFR 211.180(a)).

Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).